Evidence map›Paper›PMID 30606734›Full record

ArticleMolecular & cellular proteomics : MCP2019

Changes in Synaptic Proteins Precede Neurodegeneration Markers in Preclinical Alzheimer's Disease Cerebrospinal Fluid.

Alberto Lleó, Raúl Núñez-Llaves, Daniel Alcolea, Cristina Chiva, Daniel Balateu-Paños, Martí Colom-Cadena, Gemma Gomez-Giro, Laia Muñoz, Marta Querol-Vilaseca, Jordi Pegueroles and 13 more

Open access · hybridAbstract read
In one paragraph

Article in Molecular & cellular proteomics : MCP, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
113citing papers in PubMed, 3 pooled it
18.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

113 citing papers in PubMed, 3 syntheses or guidelines pooled it, 247 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Preclinical and clinical biomarker studies of CT1812: A novel approach to Alzheimer's disease modification.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2021
    Trial
  5. Article
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  8. Review
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  10. Review
  11. Differences in blood levels of neuroligin-derived peptides in a cohort for early detection of Alzheimer's disease.The journals of gerontology. Series A, Biological sciences and medical sciences · 2026
    Article
  12. Plasma Proteomic Analysis ofmedRxiv : the preprint server for health sciences · 2026
    Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Cerebrospinal fluid NPTX2 and [Alzheimer's research & therapy · 2025
    Article
  19. Article
  20. Article

53 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors at 7 institutions in 2 countries.

Alberto LleóFrom the ‡Memory Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain; alleo@santpau.cat.
Raúl Núñez-Llaves§Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 28031 Madrid, Spain.
Daniel AlcoleaFrom the ‡Memory Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain.
Cristina Chiva‖Proteomics Unit, Center for Genomics Regulation, Barcelona Institute of Science and Technology, 08003 Barcelona.ORCID 0000-0001-8150-6203
Daniel Balateu-Paños¶Biomedical Research Institute Sant Pau (IIB Sant Pau), 08025Barcelona, Spain.ORCID 0000-0003-2893-7738
Martí Colom-Cadena§Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 28031 Madrid, Spain.
Gemma Gomez-Giro¶Biomedical Research Institute Sant Pau (IIB Sant Pau), 08025Barcelona, Spain.
Laia Muñoz§Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 28031 Madrid, Spain.
Marta Querol-Vilaseca§Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 28031 Madrid, Spain.
Jordi Pegueroles§Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 28031 Madrid, Spain.
Lorena Rami‡‡Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Department, Hospital Clínic-Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), 08015 Barcelona, Spain.
Albert Lladó‡‡Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Department, Hospital Clínic-Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), 08015 Barcelona, Spain.
José L Molinuevo‡‡Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Department, Hospital Clínic-Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), 08015 Barcelona, Spain.
Mikel Tainta§§Department of Neurology, Center for Research and Advanced Therapies, CITA-Alzheimer Foundation, 20009 San Sebastian, Spain.
Jordi Clarimón§Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 28031 Madrid, Spain.
Tara Spires-Jones‖‖Centre for Discovery Brain Sciences and UK Dementia Research Institute, University of Edinburgh EH8 9JZ, UK.
Rafael BlesaFrom the ‡Memory Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain.
Juan ForteaFrom the ‡Memory Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain.ORCID 0000-0002-1340-638X
Pablo Martínez-Lage§§Department of Neurology, Center for Research and Advanced Therapies, CITA-Alzheimer Foundation, 20009 San Sebastian, Spain.ORCID 0000-0001-5404-9967
Raquel Sánchez-Valle‡‡Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Department, Hospital Clínic-Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), 08015 Barcelona, Spain.
Eduard Sabidó‖Proteomics Unit, Center for Genomics Regulation, Barcelona Institute of Science and Technology, 08003 Barcelona.
Àlex Bayés***Molecular Physiology of the Synapse Laboratory, Biomedical Research Institute Sant Pau (IIB Sant Pau), 08025, Barcelona, Spain.ORCID 0000-0002-5265-6306
Olivia Belbin§Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 28031 Madrid, Spain; obelbin@santpau.cat.ORCID 0000-0002-6109-6371
Hospital de Sant Pau · ESConsorci Institut D'Investigacions Biomediques August Pi I Sunyer · ESUniversitat Pompeu Fabra · ESFundacion CITA Alzheimer · ESOsakidetza · ESUK Dementia Research Institute · GBUniversitat Autònoma de Barcelona · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

A biomarker of synapse loss, an early event in Alzheimer's disease (AD) pathophysiology that precedes neuronal death and symptom onset, would be a much-needed prognostic biomarker. With direct access to the brain interstitial fluid, the cerebrospinal fluid (CSF) is a potential source of synapse-derived proteins. In this study, we aimed to identify and validate novel CSF biomarkers of synapse loss in AD. Discovery: Combining shotgun proteomics of the CSF with an exhaustive search of the literature and public databases, we identified 251 synaptic proteins, from which we selected 22 for further study. Verification: Twelve proteins were discarded because of poor detection by Selected Reaction Monitoring (SRM). We confirmed the specific expression of 9 of the remaining proteins (Calsynytenin-1, GluR2, GluR4, Neurexin-2A, Neurexin-3A, Neuroligin-2, Syntaxin-1B, Thy-1, Vamp-2) at the human synapse using Array Tomography microscopy and biochemical fractionation methods. Exploration: Using SRM, we monitored these 9 synaptic proteins (20 peptides) in a cohort of CSF from cognitively normal controls and subjects in the pre-clinical and clinical AD stages (

Indexed as

AgedAlzheimer DiseaseAutopsyBiomarkersCalcium-Binding ProteinsEarly DiagnosisFemaleHumansMaleNerve Tissue ProteinsProdromal SymptomsPrognosisProteomicsReceptors, AMPASynapsesSyntaxin 1BiomarkersCalcium-Binding ProteinsCLSTN1 protein, humanglutamate receptor ionotropic, AMPA 4Nerve Tissue Proteinsneurexin IIIalphaReceptors, AMPASTX1B protein, humanSyntaxin 1Thy-1 AntigensAlzheimer's diseaseBiomarker: PrognosticCerebrospinal fluidClinical proteomicsSelected reaction monitoring

Identifiers

PMID30606734
PMCPMC6398205
OpenAlexW2907592852

What OpenQuestion holds

Textmetadata
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.